Document Detail

Proteomic analysis of lung tissues from patients with pulmonary arterial hypertension.
MedLine Citation:
PMID:  21041689     Owner:  NLM     Status:  In-Process    
BACKGROUND: Pulmonary arterial hypertension is a disorder of vascular remodeling causing increased resistance to pulmonary blood flow. The expression of proteins in lungs from pulmonary arterial hypertension patients was investigated in an unbiased approach to further understand the pathobiology of this disease.
METHODS AND RESULTS: Label-free liquid chromatography tandem mass spectrometry was used to compare protein profiles in surgical samples of lungs from 8 patients with pulmonary arterial hypertension and 8 control subjects. More than 300 proteins were detected. On the basis of robust criteria, the levels of 25 proteins varied between the 2 groups. The majority of upregulated proteins were associated with cell growth, proliferation, and cell metabolism. Novel findings included an increased expression of chloride intracellular channel 4, receptor for advanced glycation end products, and periostin. Increased expression of chloride intracellular channel 4, a multifunctional protein involved in angiogenesis, and several signaling pathways implicated in pulmonary arterial hypertension--transforming growth factor-β, vascular endothelial growth factor, and bone morphogenetic protein--was confirmed by Western blotting and localized predominantly to endothelial cells in occlusive and plexiform vascular lesions.
CONCLUSIONS: Label-free proteomics identified differences in the expression of several proteins in the pulmonary arterial hypertension lung, many of which are relevant to the disease process. Increased expression of chloride intracellular channel 4 may be pertinent to the disorganized angiogenesis of plexiform lesions.
Vahitha B Abdul-Salam; John Wharton; John Cupitt; Mark Berryman; Robert J Edwards; Martin R Wilkins
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-11-01
Journal Detail:
Title:  Circulation     Volume:  122     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2058-67     Citation Subset:  AIM; IM    
Centre for Pharmacology and Therapeutics, Department of Medicine, Imperial College London, London, UK.
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Grant Support
//British Heart Foundation

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